Epidermolysis Bullosa

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Article initiated by:

Allison Umfress, MD

All contributors:

Jullian Valadez, Colleen Halfpenny, M.D., S. Grace Prakalapakorn, MD, MPH, Allison Umfress, MD, Maria D. Bernal, MD

Assigned editor:

Maria D. Bernal, MD, Allison Umfress, MD

Review:

Assigned status Up to Date

 by Maria D. Bernal, MD on December 31, 2024.

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Contributing Editors:	add

Summary

Epidermolysis bullosa is group of inherited dermatoses characterized by dysfunction at the Dermal-epidermal junction that predisposes individuals to increased damage from mechanical trauma. There are 34 epidermolysis bullosa subtypes organized within four major inherited groups. Epidermolysis bullosa acquisita is extremely rare and different from the other types. Epidermolysis bullosa acquisita is thought to be an autoimmune disease and begins at age 30's or 40's unlike the other types of Epidermolysis bullosa, which begin at birth or shortly thereafter. Patients with Epidermolysis bullosa have mucosal and skin fragility and can present with numerous ocular manifestations involving the conjunctiva, cornea and eyelids. The ophthalmic complications vary with each subtype and treatment options can be complicated as the disease often presents in childhood and is chronic. These patients will often present to pediatric ophthalmology clinics for routine screening or with complications of the disease such as corneal abrasions, corneal scarring, corneal ulceration, symblepharon formation, and complications from eyelid scarring such as ectropion, entropion, or trichiasis. The management of these patients requires a multidisciplinary approach.

Subtypes of Disease

There are 34 epidermolysis bullosa subtypes organized within four major inherited groups:

1. Epidermolysis Bullosa Simplex (14 subtypes),
2. Junctional Epidermolysis Bullosa (9 subtypes)
3. Dystrophic Epidermolysis Bullosa (11 subtypes)
4. Kindler Epidermolysis Bullosa (about 250 case reports worldwide).
   
5. The classifications are distinguished based on the anatomic location of disease in the cutaneous basement membrane zone, with Epidermolysis Bullosa Simplex occurring more superficially, Junctional Epidermolysis Bullosa occurring at the lamina lucida (between the basal cell plasma membrane and plasma densa), Dystrophic Epidermolysis Bullosa occurring below the lamina densa (with absent or reduced anchoring fibrils), and Kindler Epidermolysis Bullosa occurring at multiple levels.

Genetics

Epidermolysis Bullosa is a rare heterogeneous disease with a wide spectrum in severity, different inheritance patterns and with more than 16 causal genes. Mutations in the affected genes lead to alterations of proteins that are key to the structure of the epidermis, basement membrane area and upper part of the dermis. Generally, Epidermolysis Bullosa Simplex is inherited in an Autosomal Dominant fashion, Junctional Epidermolysis Bullosa is inherited in an autosomal recessive fashion, Dystrophic Epidermolysis Bullosa has been described to be inherited in both an Autosomal dominant and recessive fashion and Kindler Syndrome is recessively inherited.

Ocular Manifestations

Ocular involvement may be present in all Epidermolysis Bullosa subtypes. However, it is more frequent and severe in Recessive Dystrophic Epidermolysis Bullosa, Junctional Epidermolysis Bullosa, Kindler Epidermolysis Bullosa and severe forms of Epidermolysis Bullosa Simplex. Ocular involvement is frequent in Epidermolysis Bullosa and can cause irreversible damage if not properly managed. The periocular and ocular surfaces are subject to similar shearing and blistering effects. Ocular abnormalities in Epidermolysis Bullosa maybe acute or chronic, symptomatic or asymptomatic, and of variable clinical severity. Age of onset of presentation of ocular involvement is highly variable and can be as early as 1 month old. Most ocular involvement in Epidermolysis Bullosa affects the eyelids, conjunctiva, cornea and tear ducts. Corneal involvement can ultimately lead to limbal stem cell deficiency and non healing corneal epithelial defects. Ocular complications may lead to refractive errors, strabismus and amblyopia. The main ocular symptoms in Epidermolysis Bullosa are red watery eyes, photophobia and ocular pain. The most common ocular findings are corneal problems (recurrent corneal erosions, abrasions, scarring, neovascularization), ectropion and eyelid blistering.

Other associated ocular symptoms reported with Dystrophic Epidermolysis Bullosa : Meibomian Gland Cysts, Iris Cysts, Retinal Detachment, Focal loss of Retinal Pigment Epithelium, Blepharitis, Lid Ulceration, Madarosis, Lagophthalmos, Irregular Astigmatism, Conjuctivocorneal blisters, Cicatricial Conjunctivitis, Symblepharon, Lacrimal Stenosis

Ocular Treatment

The mainstay of ophthalmic treatment is ocular surface lubrication with preservative free lubricants to prevent and protect corneal and mucous membrane erosion.

Early ocular intervention is recommended in patients with Epidermolysis Bullosa, as minor friction can cascade into corneal damage and ultimate visual acuity loss. Given that disease manifestation can occur as early as infancy, prompt recognition and treatment of sight-threatening processes such as corneal abrasion or symblepharon is crucial to preserve sight- with some patients responding well to surgical interventions like lamellar keratectomy and symblepharon lysis and amniotic membrane transplantation. Eyelid scrubs should not be used as they can cause eyelid blisters. Other documented symptoms such as cataracts (seen across a variety of ages) and ectropion (due to blistering around eyelids) should be treated as encountered, with care that perioperative course and even simple measures such as glasses wearing can cause blistering. Subtype-specific approaches are also important, as some techniques focused on treating the junctional epidermolysis bullosa of Herlitz utilize keratinocyte autografts for complete blister healing prior to ectropion repair.

Systemic treatment

Symptomatic disease treatment has been the mainstay modality of controlling the disease, principally via avoiding trauma and good wound care and disinfection. Close follow up with an interdisciplinary team and preventive measures from the patient are important.

In managing systemic symptoms, trials assessing topical and systemic treatments have been conducted. Systemic Mycophenolate mofetil, cyclosporine, granulocyte colony stimulating factor injection, and systemic apremilast small trials with some response have ben published . Bone marrow transplantation has been assessed but has high mortality rate due to immunosuppression and intravenous mesenchymal stem cells have been successful but without long term effects. Innovative therapeutic treatments aim at modifying the disease course of Epidermolysis Bullosa with gene therapy are encouraging. Losartan maybe useful as a first line therapy for Recessive Dystrophic Epidermolysis Bullosa to delay fibrotic changes.

Follow Up

Follow-up with specialists should be pursued based on disease manifestations and baseline measurements for certain conditions , but the primary managers of the disease condition should be a primary care physician in unison with a dermatologist with long term follow up to provide the best outcomes All patients should be referred to an ophthalmologist for a baseline examination and followed as necessary.

Prognosis

Prognosis varies based on disease subtype and complications from disease manifestations.Thus, life expectancy can range from normal in milder disease manifestations/subtypes to mortality; the third to fifth decade of life following skin cancer development; and as early as childhood in severe junctional epidermolysis cases.